Protocol for Stereoselective Construction of Highly Functionalized Dienyl Sulfonyl Fluoride Warheads

A pyrrolidine-mediated
Knoevenagel-type reaction for highly stereoselective
construction of novel α-halo-1,3-dienylsulfonyl fluorides was
achieved in up to 100% Z-selectivity and high yields
at room temperature from condensation of the readily available aldehydes
and halomethanesulfonyl fluorides. This protocol provided a class
of unique α-halo-1,3-dienylsulfonyl fluorides with wide scope
and excellent functional group compatibility. The α-halo-1,3-dienylsulfonyl
fluorides were used as versatile building blocks in sulfur fluoride
exchange click chemistry, Suzuki reaction, and Sonogashira reaction
for the assembly of highly functionalized dienyl sulfonyl fluoride
derivatives to be applied as covalent warheads for the discovery of
new drugs.